Polyethylene glycol-superoxide dismutase, a conjugate in search of exploitation

Our plain-English summary of Polyethylene glycol-superoxide dismutase, a conjugate in search of exploitation, by F.M. Veronese, P. Caliceti, O. Schiavon, et al (Advanced Drug Delivery Reviews, 2002).

The study

• Authors: F.M. Veronese, P. Caliceti, O. Schiavon, M. Sergi
• Journal: Advanced Drug Delivery Reviews
• Published: 2002;54(4):587-606
• Type of article: Review
• Cited by: 172 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Without a doubt PEG-SOD has been the enzyme most studied in PEGylation. One can say that it represents the preferred model to assess chemistries for PEG activation, analytical procedures suitable for conjugate characterization, the influence of PEG size in conjugate removal from circulation and elimination of immunogenicity and antigenicity, and the effect of route of administration. The effect of PEG conjugation was studied in vitro and in vivo models in comparison with the free enzyme and the following conclusions may be drawn: (1) At the blood vessel level, PEG-SOD has been shown to provide a greater resistance to oxidant stress, to improve endothelium relaxation and inhibit lipid oxidation. (2) In the heart, PEG-SOD proved to be at least as effective as native SOD in treatment of reperfusion-induced arrhythmias and myocardial ischemia. (3) In the lung, PEG-SOD appeared to be able to reduce oxygen toxicity and E. coli-induced lung injury, but not in the treatment of lung physiopathology associated with endotoxin-induced acute respiratory failure and in the reduction of asbestos-induced cell damage. (4) On cerebral ischemia/reperfusion injuries the effect of PEG-SOD was uncertain, also due to the difficulty of cerebral cell penetration. (5) In kidney and liver ischemia both enzyme forms were found to ameliorate reperfusion damage. In view of so much positive research on PEG-SOD, it is surprising that no approved application in human therapy has been established and approved.

In plain English

This article was a review, not a new study. The authors surveyed published laboratory and animal research on PEG–SOD, the antioxidant enzyme superoxide dismutase chemically linked to polyethylene glycol. They covered how it is made and tested and its effects on blood vessels, heart, lungs, brain, kidneys and liver. Asbestos came up in one reviewed rat study by Mossman, which used an inhalation model of asbestosis in Fischer 344 rats exposed to crocidolite asbestos. In that study, PEG–SOD did not ameliorate crocidolite-induced cell injury, inflammation or accumulation of hydroxyproline in the lung, whereas PEG–catalase did inhibit asbestos-induced cell damage and inflammation. The authors read these studies as suggesting that an oxidant such as hydrogen peroxide is involved in the development of asbestosis. Elsewhere in the lung, the reviewed studies suggested PEG–SOD reduced oxygen toxicity and E. coli-induced lung injury. The authors noted it was surprising that no approved use of PEG–SOD in human therapy had been established. They also said they did not review every paper on the subject.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: review of published laboratory (in vitro) and animal (in vivo) studies of PEG–SOD
• Who was studied: Published studies of PEG–SOD in cell cultures and in animals (including rats, guinea-pigs, rabbits, dogs, pigs and piglets). The asbestos-related study reviewed used Fischer 344 rats.
• Exposure: The main subject was treatment with PEG–SOD (and, in some studies, PEG–catalase). The asbestos exposure in the reviewed Mossman study was inhaled crocidolite asbestos in rats. Reviewed cell studies used cells exposed to crocidolite asbestos.
• Main results:
  • In the reviewed rat inhalation study (Mossman), PEG–SOD did not ameliorate crocidolite-induced cell injury, inflammation or hydroxyproline accumulation in the lung.
  • In the same reviewed rat study, PEG–catalase did inhibit asbestos-induced cell damage and inflammation.
  • The authors interpreted these asbestos studies as suggesting that an oxidant more reduced than superoxide anion, such as hydrogen peroxide, is involved in the development of asbestosis.
  • Reviewed cell-culture studies reported that adding antioxidants prevented cytotoxicity in cells exposed to crocidolite asbestos.
  • In the lung, the reviewed studies suggested PEG–SOD could reduce oxygen toxicity and E. coli-induced lung injury, but not lung changes linked to endotoxin-induced acute respiratory failure.
  • In the heart, the reviewed studies found PEG–SOD at least as effective as native SOD against reperfusion-induced arrhythmias and myocardial ischemia.
• The authors' conclusion: The authors concluded that, despite much positive research, it was surprising that no approved application of PEG–SOD in human therapy had been established.
• Limitations the authors state:
  • The authors stated that they did not review all of the papers on PEG–SOD.

Topics

Medical terms in this study, explained in our Lexicon: Superoxide.

Related studies

• Inhibition of lung injury, inflammation, and interstitial pulmonary fibrosis by polyethylene glycol-conjugated catalase in a rapid inhalation model of asbestosis — B.T. Mossman, J.P. Marsh, et al. (1990)
• Approaches to prevention of asbestos-induced lung disease using polyethylene glycol (PEG)-conjugated catalase — B.T. Mossman, J.P. Marsh, et al. (1986)
• Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma — K. Kahlos, S. Anttila, et al. (1998)
• Leukocyte-derived extracellular superoxide dismutase does not contribute to airspace EC-SOD after interstitial pulmonary injury — M.L. Manni, M.W. Epperly, et al. (2012)
• Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan — F. Gao, J.R. Koenitzer, et al. (2008)
• Extracellular superoxide dismutase in pulmonary fibrosis — F. Gao, V.L. Kinnula, et al. (2008)

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